Original Article

Obesity (2007) 15, 846–852; doi: 10.1038/oby.2007.595

Differential Lipolytic Regulation in Human Embryonic Stem Cell–derived Adipocytes*

Vanessa van Harmelen*, Gaby Åström*, Amy Strömberg, Eva Sjölin*, Andrea Dicker*, Outi Hovatta and Mikael Rydén*

  1. *Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
  2. Department of Clinical Science, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.

Correspondence: Vanessa van Harmelen Department of Medicine, M61, Karolinska University Hospital, Huddinge 141 86, Stockholm, Sweden. E-mail: vanessa.van.harmelen@ki.se

*The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 24 August 2006; Revised  00; Accepted 24 October 2006.

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Abstract

Objective: Human embryonic stem cells (hESCs) have raised great hopes for future clinical applications. Several groups have succeeded in differentiating hESCs into adipocytes, as determined by morphology, mRNA expression, and protein secretion. However, determination of lipolytic response, the most important characteristic of adipocytes, has not been performed. This work was intended to study adipogenic conversion of hESCs by functional assessment of differentiation.

Research Methods and Procedures: Single undifferentiated colonies were allowed to transform into embryonic bodies. mRNA expression for a set of adipocyte-specific genes and leptin/adiponectin secretion and lipolysis were assessed at different time-points after differentiation.

Results: In contrast to primary human adipocytes, hESC-derived adipocytes showed a very small response to classical beta-adrenergic agonists, although they expressed the major genes in the lipolytic cascade. In contrast, there was a significant lipolytic response to atrial natriuretic peptide.

Discussion: Although hESC-derived adipocytes seem to be morphologically and expressionally similar to mature adipocytes, there are important functional differences that could depend on their early developmental origin. We conclude that, in contrast to mature adipocytes, hESC-derived adipocytes display a differential response to atrial natriuretic peptide and catecholamines.

Keywords:

glycerol, catecholamines, hormone-sensitive lipase, adipocytes, lipolysis

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